The immune system dependency of the protein corona

Abstract

Biomedical applications of nanocarriers are a research field with increasing focus within the scientific community. Through the blood stream, nanocarriers may transport drugs or reporter molecules to specific cells or tissues without exposing them to other parts of the organism. Upon interactions of nanocarriers with blood proteins, a protein corona is formed. These interactions with proteins tremendously influence the properties and behavior of nanocarriers in biological media. In order to achieve applicable nanomedicines, control over the protein corona is required. The blood composition of individuals varies vastly based on constitution, environmental conditions and nutrition. Immunoglobulins are a protein class that is particularly affected by the individual state of the immune system. Therefore, the aim of this work is to investigate the interactions nanocarriers undergo with different immunoglobulins and how varrying immunoglobulin concentrations in blood plasma affect the protein corona. First, the interactions, which differently charged polymeric nanoparticles undergo with different immunoglobulins in the form of IgG, IgA, and IgM were investigated. Each immunoglobulin class showed different binding parameters to the different nanoparticles and in some cases induced aggregation processes. All immunoglobulins appeared denatured on the surface of nanoparticles with the possible consequence of unwanted reactions of the immune system. Afterwards, the protein corona of different nanocarriers was compared after incubation in pooled blood plasma and blood plasma of varied, physiologically relevant immunoglobulin concentrations. For this, averaged plasma was modified by increasing IgG, IgA, or IgM or by decreasing the IgG concentration. In all four cases, a significant alteration of the protein corona was observed. The promoted adsorption of IgG in IgG-enriched plasma was further analyzed and resulted in a promoted uptake in macrophages. The effects of IgG-enriched plasma on the protein corona could be prevented successfully by pre-incubation of nanocarriers with the protein clusterin. Finally, poly(ethylene glycol)-binding IgG was quantified in blood plasma and the protein corona of different nanocarriers. It could be observed, that the concentration of these antibodies was relatively high on nanocarriers containing poly(ethylene glycol)-chains on their surface. In conclusion, further understanding of the complex interactions nanocarriers undergo with blood proteins with special regards to immunoglobulins was gained. By pre-incubation with clusterin, nanocarriers behave more independent on the individual blood composition.